Socio-demographic factors, reproductive history and risk of osteoarthritis in a cohort of 4.6 million Danish women and men.

OBJECTIVE: Studies addressing possible socio-demographic and reproductive factors in the aetiology of osteoarthritis (OA) are few. We studied possible influences of educational level, household income, marital status and parenting patterns on OA risk overall and at anatomical sites. METHOD: We linked national register data about socio-demographic variables, reproductive histories and OA hospital contacts to a cohort of 4.6 million Danes. Ratios of first OA hospitalisation rates (RRs) were calculated using Poisson regression. RESULTS: Overall, 100,437 women and 92,020 men had a first OA hospital contact during 91.5 million person-years between 1982 and 2008. Short education, low income and married status were significantly associated with increased OA risk, and persons with children were at higher risk of OA(overall) (RR=1.10 in women; RR=1.22 in men), OA(knee) (RRs 1.14; 1.28), OA(back) (RRs 1.18; 1.33), and OA(hand) (RRs 1.21; 1.43), but not of OA(hip) (RRs 0.96; 1.00) than persons without children. The RR of OA(overall) increased by a factor of 1.05 in women and 1.04 in men per additional child, most notably for OA(knee) in women (1.10 per child). CONCLUSION: Risk of OA hospitalisation was highest among married persons and persons with short education or low income. The similar or even stronger associations with reproductive factors in men than women suggest that unmeasured lifestyle factors rather than biological factors associated with pregnancy might explain the higher OA risk in persons with children. However, the particularly strong association between parity and risk of OA(knee) in women is compatible with a role of pregnancy-associated factors.

National cohort study of reproductive risk factors for rheumatoid arthritis in Denmark: a role for hyperemesis, gestational hypertension and pre-eclampsia?

OBJECTIVES: While reproductive factors might plausibly be involved in the aetiology of rheumatoid arthritis (RA), the female predominance remains unexplained. A study was undertaken to address the possible impact of live births, pregnancy losses and pregnancy complications on the subsequent risk of RA in a nationwide cohort study. METHODS: National register data were used to link reproductive histories and later RA hospitalisations in a cohort of 4.4 million Danes. As a measure of relative risk associated with different reproductive histories, ratios of first inpatient RA hospitalisation rates (RRs) were used with 95% confidence intervals (CIs) obtained by Poisson regression analysis. RESULTS: Overall, 7017 women and 3041 men were admitted to hospital with RA in 1977-2004 (88.8 million person-years). The risk of RA was inversely associated with age at birth of first child in both women and men (p for trend <0.001). Overall, nulliparity and a history of pregnancy loss were not associated with RA risk but, compared with one-child mothers, women with two (RR 0.84; 95% CI 0.78 to 0.90) or three (RR 0.83; 95% CI 0.77 to 0.91) children were at reduced risk. The risk of RA was increased in women with a history of hyperemesis (RR 1.70; 95% CI 1.06 to 2.54), gestational hypertension (RR 1.49; 95% CI 1.06 to 2.02) or pre-eclampsia (RR 1.42; 95% CI 1.08 to 1.84). CONCLUSIONS: One-child mothers and young parents are at increased risk of RA later in life, possibly due to socioeconomic factors. The novel finding of a significantly increased risk of RA in women whose pregnancies were complicated by hyperemesis, gestational hypertension or pre-eclampsia might reflect reduced immune adaptability to pregnancy in women disposed to RA or a role of fetal microchimerism in the aetiology of RA.

Cytokines, autoantibodies and viral antibodies in premorbid and postdiagnostic sera from patients with rheumatoid arthritis: case-control study nested in a cohort of Norwegian blood donors.

OBJECTIVE: To assess the timing of changes in cytokines, cytokine-related markers, autoantibodies and viral antibodies in the pathogenesis of rheumatoid arthritis (RA). METHODS: Case-control study nested in a prospective cohort of 31 330 blood donors in Oslo, Norway. Forty-nine donors developed RA up to 23 years after their most recent blood donation. Stored sera from these donors (case sera) and a sex- and age-matched sample of 245 healthy donors (control sera), and postdiagnostic sera from 33 of the 49 RA cases, were analysed for a panel of cytokines and cytokine-related markers, autoantibodies and antibodies against Epstein-Barr virus and parvovirus B19. RESULTS: Cytokines and cytokine-related markers were generally negative in case sera from >5 years before the diagnosis of RA. In the 5-year interval immediately before the diagnosis of RA, more case than control sera were positive (odds ratios >2) for interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor antagonist, IL-4, IL-10, tumour necrosis factor-alpha and soluble tumour necrosis factor receptor I. In postdiagnostic sera, however, 11 of 16 examined cytokines and cytokine-related markers were statistically significantly elevated compared with control sera. Seropositivity for IgG antibodies against cyclic citrullinated peptides and for IgM and IgA rheumatoid factors were seen in case sera from up to 18 years before the diagnosis of RA. IgG antibodies against Epstein-Barr virus and parvovirus B19 did not differ significantly between case and control sera. CONCLUSIONS: Cytokines and cytokine-related markers appear to be upregulated rather late in RA pathogenesis. In contrast, IgM rheumatoid factor and IgG anti-cyclic citrullinated peptide autoantibodies may precede the diagnosis of RA by up to two decades.

The use of adjunctive antipsychotics to treat depression in UK primary care.

OBJECTIVE: Adjunctive antipsychotic therapy can be prescribed to patients with depression who have inadequate response to antidepressants. This study aimed to describe the use of adjunctive antipsychotics over a time period that includes the authorization in 2010 of prolonged-release quetiapine as the first adjunct antipsychotic to be used in major depressive disorder in the UK. RESEARCH DESIGN AND METHODS: Adults with an episode of depression between January 1, 2005 and July 31, 2013 were identified from antidepressant prescriptions and depression diagnoses in the UK Clinical Practice Research Datalink. Patients with prior records of bipolar disorder, schizophrenia, or antipsychotic prescriptions were excluded. MAIN OUTCOME MEASURES: Rates of adjunct antipsychotic initiation and characteristics and management of patients with adjunct antipsychotics. RESULTS: Of 224,353 adults with depression, 5,807 (2.6%) initiated adjunct antipsychotic therapy. Overall incidence of antipsychotic initiation was 7.4 per 1,000 patient-years (95% CI = 7.2-7.6). Between 2005-2013, the overall rate did not change, although initiation of typical antipsychotic prescribing decreased (57.7% to 29.1%), while atypical antipsychotics, especially quetiapine (14.1% to 49.7%), increased. Of those who initiated antipsychotics, 59.4% were women (typical antipsychotics = 62.8%, atypical antipsychotics = 56.1%) and median age was 46 years (typicals = 49 years, atypicals = 44 years). CONCLUSIONS: Antipsychotics were rarely used to treat depression between 2005-2013 in UK primary care. The choice of adjunctive antipsychotic therapy changed over this time, with atypical antipsychotics now representing the preferred treatment choice. However, information on patients strictly cared for in other settings, such as by psychiatrists or in hospitals, potentially more severe patients, was unavailable and may differ. Nonetheless, the high off-label use in primary care, even after the authorization of quetiapine, suggests that there is a need for more licensed treatment options for adjunctive antipsychotic therapy in major depressive disorder.